Copper-64 (T1/2 = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. octreotide, a somatostatin receptor ligand. has been conjugated with TETA and CPTA, labeled with 64Cu. evaluated both in vitro and in vivo and compared to 111 in-DTPA-D-Phe1-octreotide. Methods: The carboxylic acid moieties on theT bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the linking agents hydroxybenzotriazol (HOBT) and diisopropylcabodiimide (DC). Receptor binding assays on all three radiolabeled octreotide conjugates were accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo biodistribution was performed using normal Sprague-Dawley rats and Lewis rats carrying a somatostatin receptor-positive rat pancreatic tumor. Results: The binding affinities of 64Cu-CPTA-D-Phe1-octreoitde and 64Cu-TETA-D-phe1-octreotide in AtT20 cell membranes were both greater than 1111n-DTPA-fl-Phe1- octreotide (Kd1 78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1-octreotide was localized primarily in the liver. Copper-64-TETA-Dphe1-octreotide, similar to 111ln-DTPA-D-Phe-octreotide, had moderate uptake in the kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948 pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64-Cu-TETA-D-Phe1-octreotide had uptake in tumors comparable to or better than llln-DTPA-D-Phe1-octreotide. conclusion: Of the two 64Cu-labeled octreotide conjugates evaluated, 64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64-TETA-D-Phe1 -octreotide binds to the somatostatin receptor with five times the affinity of 111ln-octreotide, has desirable clearance properties (renal clearance with rapid excretion) and is a potential agent for PET imaging of somatostatin receptors.